The role of nitric oxide in theregulation of colonic water andelectrolyte transport in normalcolon and during acetic acidexperimental colitis in rats
T.M. Savka, G.M Tolstanova, Ja.M. Savitsky,V.I. Kimakovich.
Danylo Galytskyi Lviv National University;Taras Shevchenko Kyiv National University
Despite numerous studies about the role of NO in the regulation of intestinal water and ion transport, the data about colonic fluid movement are controversial and scanty. The aim of the present study was to investigate the contribution of NO in the basal net water and electrolytes (Na+, K+, Cl-) transport in normal colon and during experimental ulcerative colitis in rats. The net water and electrolytes movements were evaluated by isolated colonic loop perfusion technique in vivo on anaesthetized male Wistar rats. Experimental colitis was modeled by rectal injection of 1 ml 4% acetic acid. In the present study, precursor of NO L-arginine (500 mg/kg, i.p.) had no effect on net water,K+ and Cl- transport, but significantly decreased (P<0.05) Na+ absorption. Injection of inhibitor NOS L-NAME (10mg/kg, i.v.) did not affect the net water and СI- movement, but induced elevation of the net Na+ absorption and a slight amelioration of K+ secretion with a significant difference P<0.01. We found profound downregulation of net water, Na+ absorption and K+ secretion which were associated with colonic mucosal ulceration at 3rd day after acetic acid introduction. Despite restoration of colonic mucosae at 7th day, Na+ absorption was not restored completely, moreover K+ secretion was still significantly decreased (P<0.01). L-arginine administration decreased the net Na+ absorption and didn’t affect the net water, K+ and Cl-movement at 1st and 3rd days after acetic acid enema. L-NAME slightly increased the net Na+ absorption (P<0.01) only at 1st day and had any effect at 3rd day. Conclusion: NO might have slight pro-secretory influence on colonic fluid transport in vivo via regulation of Na+ and K+ transport.
nitric oxide, ion transport, water transport, colon,ulcerative colitis
- Перший національний конгрес з біоетики // Ежене-дельник АПТЕКА. - 2001. - №37 (308) (від 24.09.2001).
- Aizman R., Brismar H., Celsi G. Nitric oxide inhibits potassium transport in the rat distal colon // Amer. J. Physiol. - 1999. - 276. - G146-154.
- Beck P.L., Li Y, Wong J., Chen C.W. et al. Inducible nitric oxide synthase from bone marrow-derived cells plays a critical role in regulating colonic inflammation/ / Gastroenterology. - 2007. - 132. - P.1778-1790.
- Bell C.J., Gall D.G., Wallace J.L. Disruption of colonic electrolyte transport in experimental colitis // Amer. J. Physiol. - 1995. - 268. - G622-630.
- DuVall M.D., Zhu S., Fuller C.M., Matalon S. Peroxynitrite inhibits amiloride-sensitive Na+ currents in Xenopus oocytes expressing -rENaC // Amer. J. Physiol. Cell Physiol. - 1998. - 274. - C1417-C1423.
- Ekblad E., Mulder H., Uddman R., Sundler F. NOS-containing neurons in the rat gut and coeliac ganglia // Neuropharmacology. - 1994. - 33. - P.1323-1331.
- Eutamene H., Theodorou V., Fioramonti J., Bueno L. Implication of NK1 and NK2 receptors in rat colonic hypersecretion induced by interleukin 1 beta: role of nitric oxide // Gastroenterology. - 1995. - 109. - P.483-489.
- Gдbel G., Garz B., Ahrens F., Aschenbach J.R. Effect of nitric oxide on electrolyte transport across the porcine proximal colon // J Comp Physiol [B]. - 2003. -173. - P.177-186.
- 9. Green C.L., Ho W., Sharkey K.A., McKay D.M. Dex-tran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO // Amer. J. Physiol. Gastroint. Liver Physiol. - 2004. -287. - G706-714.
- 10. Guo Y., DuVall M.D., Crow J.P., Matalon S. Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers // Amer. J. Physiol Lung Cell Mol Physiol. - 1998. - 274. - L369-377.
- Hawker P.C., McKay J.S., Turnberg L.A. Electrolyte transport across colonic mucosa from patients with inflammatory bowel disease // Gastroenterology. -1980. - 79. - P.508-511.
- Jain L., Chen X.J., Brown L.A., Eaton D.C. Nitric oxide inhibits lung sodium transport through a cGMP-mediated inhibition of epithelial cation channels // Amer. J. Physiol. Lung. Cell Mol. Physiol. - 1998. - 274. -L475-484.13. Kankuri E., Hдmдlдinen M., Hukkanen M. et al. Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis // Scand. J. Gastroenterol. - 2003. - 38. - P.186-192.
- Kolios G., Rooney N., Murphy C.T. et al.Expression of inducible nitric oxide synthase activity in human colon epithelial cells: modulation by T lymphocyte derived cytokines // Gut. - 1998. - 43. - P.56-63.
- MacNaughton W.K,. Lowe S.S., Cushing K. Role of nitric oxide in inflammation-induced suppression of secretion in a mouse model of acute colitis // Amer. J. Physiol. - 1998. - 275. - G1353-1360.
- Martнn M.C., Martinez A., Mendoza J.L. et al. Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility // Immunogenetics. - 2007. - 59. - P.833-837.
- Myers B.S., Martin J.S., Dempsey D.T. et al. Acute experimental colitis decreases colonic circular smooth muscle contractility in rats // Amer. J. Physiol. - 1997. -273. - P.928-936.
- Ortiz PA., Garvin J.L. Role of nitric oxide in the regulation of nephron transport // Amer. J. Physiol. Renal. Physiol. - 2002. - 282. - F777-784.
- 19. Perner A., Andresen L., Normark M. et al. Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis // Gut. - 2001. - 49. - P.387-394.
- 20. Rachmilewitz D., Karmeli F., Okon E., Bursztyn M. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity // Ibid. - 1995. - 37. -P.247-255.
- Reddix R.A., Liu X., Miller M.J. et al. Constitutive nitric oxide release modulates neurally-evoked chloride secretion in guinea pig colon // Auton Neurosci. - 2000. -86. – P.47-57.
- Reddix R.A., Mullet D., Fertel R., Cooke H.J. Endogenous nitric oxide inhibits endothelin-1-induced chloride secretion in guinea pig colon // Nitric Oxide. -1998. - 2. - P.28-36.
- Reinders C.A., Jonkers D., Janson E.A. et al. Rectal nitric oxide and fecal calprotectin in inflammatory bowel disease // Scand. J. Gastroenterol. - 2007. - 42. -P.1151-1157.
- Roediger W.E. Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis // Aliment. Pharmacol. Therap. - 2008. - 27. - P.531-541.
- Schedl H.P., White D. Use of polyethylene glycol and phenol red as unabsorpabed indicators for intestinal absorption studies in man // Gut. - 1966. - 7, № 2. -P.159-163.
- Schultheiss G., Seip G., Kocks S.L., Diener M. Ca(2+)-dependent and -independent Cl(-) secretion stimulated by the nitric oxide donor, GEA 3162, in rat colonic epithelium // Eur. J. Pharmacol. - 2002 - 444. - P.21-30.
- Seril D.N., Liao J., Yang G.Y. Colorectal carcinoma development in inducible nitric oxide synthase-defi-cient mice with dextran sulfate sodium-induced ulcerative colitis // Mol. Carcinog. - 2007. - 46. - P.341-353.
- Sladen G.E., Dawson A.M. An evaluation of perfusion techniques in the study of water and electrolyte absorption in man: the problem of endogenous secretions // Gut. - 1968. - 9. - P.530-535.
- 29. Sladen G.E., Harries J.T. Studies on the effects of unconjugated dyhidroxy bile salts on rat small intestinal function in vivo // Biochem. Biophys. Acta. - 1972. -288. - P.443-456.
- 30. Wilson K.T., Xie Y., Musch M.W., Chang E.B. Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon // J. Pharmacol. Exp. Therap. - 1993. - 266. - P.224-230.